883 research outputs found
Disruption of the developmental programme of Trypanosoma brucei by genetic ablation of TbZFP1, a differentiation-enriched CCCH protein
No full textThe regulation of differentiation is particularly important in microbial eukaryotes that inhabit multiple environments. The parasite Trypanosoma brucei is an extreme example of this, requiring exquisite gene regulation during transmission from mammals to the tsetse fly vector. Unusually, trypanosomes rely almost exclusively on post-transcriptional mechanisms for regulated gene expression. Hence, RNA binding proteins are potentially of great significance in controlling stage-regulated processes. We have previously identified TbZFP1 as a trypanosome molecule transiently enriched during differentiation to tsetse midgut procyclic forms. This small protein (101 amino acids) contains the unusual CCCH zinc finger, an RNA binding motif. Here, we show that genetic ablation of TbZFP1 compromises repositioning of the mitochondrial genome, a specific event in the strictly regulated differentiation programme. Despite this, other events that occur both before and after this remain intact. Significantly, this phenotype correlates with the TbZFP1 expression profile during differentiation. This is the first genetic disruption of a developmental regulator in T. brucei. It demonstrates that programmed events in parasite development can be uncoupled at the molecular level. It also further supports the importance of CCCH proteins in key aspects of trypanosome cell function
Correction to: Assessing the quality of cardiac rehabilitation programs by measuring adherence to the Australian quality indicators
No full textFollowing publication of the original article [1], the authors identified two errors in the author names. Firstly, the two co-authors’ names J Hendriks and C Gallagher were mistakenly merged into one name ‘Hendriks Gallagher JC’. Secondly, the given name and family name were erroneously transposed. The author group has been updated above and the original article [1] has been corrected
The Impact of Phytosterols on the Healthy and Diseased Brain
No full textThe central nervous system (CNS) is the most cholesterol-rich organ in mammals. Cholesterol homeostasis is essential for proper brain functioning and dysregulation of cholesterol metabolism can lead to neurological problems. Multiple sclerosis (MS) and Alzheimer's disease (AD) are examples of neurological diseases that are characterized by a disturbed cholesterol metabolism. Phytosterols (PS) are plant-derived components that structurally and functionally resemble cholesterol. PS are known for their cholesterol-lowering properties. Due to their ability to reach the brain, researchers have started to investigate the physiological role of PS in the CNS. In this review, the metabolism and function of PS in the diseased and healthy CNS are discussed.This work was supported by grants of the Research Foundation Flanders (FWO; 12J9116N, 12JG119N, and G099618N to Tess Dierckx, Jeroen F.J. Bogie and Jerome J.A. Hendriks).Hendriks, JJA (reprint author), Hasselt Univ, Biomed Res Inst, Diepenbeek, Hassett, Belgium.
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Durability-based design: the European perspective
No full textIn Europe, design for the durability of new reinforced concrete structures is currently based on a prescriptive approach. The design, execution (construction) and planned maintenance of a concrete structure have to lead to the intended level of safety and serviceability throughout its entire service life. This requires numeric models based on a sound scientific background of mechanistic understanding as the basis for design and management tools and for the further development of standards and regulations. Designers must understand the basic deterioration mechanisms and the potential types and rates of damage development. For example, different types of corrosion cause very different damage developments, some of which reduce structural safety. We propose that the next generation of service life models should either explicitly include the propagation period or implicitly include it by selecting an accepted probability of depassivation that reflects the type of corrosion and its structural implications.</p
CNS delivery of anti-CD52 antibodies modestly reduces disease severity in an animal model for multiple sclerosis
No full textBackground and aims: Alemtuzumab is a humanized monoclonal antibody that depletes CD52-bearing B and T lymphocytes. Clinical trials defined that systemic administration of alemtuzumab reduces disease severity in the relapsing-remitting phase of multiple sclerosis (MS). However, its efficacy in progressive MS patients is limited, which may reflect the inability of alemtuzumab to cross the reconstituted BBB in these patients. Objective: to study whether central nervous system (CNS) delivery of anti-CD52 antibodies reduces disease severity and the neuroinflammatory burden in the experimental autoimmune encephalomyelitis (EAE) model. Methods: Anti-CD52 antibodies were administered intrathecally during the acute and chronic phases of EAE. Flow cytometry and immunohistochemistry were utilized to define immunological and pathological parameters. Results: We show that subcutaneously administrated anti-CD52 antibodies completely abolish EAE disease severity. CNS delivery of anti-CD52 antibodies during both the acute and chronic phases of EAE moderately reduces disease severity and the neuroinflammatory burden. Our findings further suggest that CNS delivery of anti-CD52 antibodies impacts both the peripheral and CNS immune cell compartments in the EAE model but not in healthy mice. Conclusion: Collectively, our findings highlight the therapeutic potential of CNS delivery of alemtuzumab for the treatment of progressive as well as early MS.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by Sanofi Genzyme, and grants of the Belgian Charcot Foundation, Research Foundation Flanders (FWO), and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).Hendriks, JJA (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Agoralaan Bldg C, B-3590 Diepenbeek, Belgium.
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A Conceptual Integrated Parametric Design Tool for Excavation Sites
No full textBuilding Information Modelling (BIM) technologies are changing the conventional structural design process. BIM level-1 and level-2 are providing guidelines and frameworks for standardization with the standard Industry Foundation Classes (IFC) and collaborative design respectively. However, the predicted full potential of BIM, BIM level-3, which is a smart design system, is still in its infancy stage. Many studies focus on single technologies that BIM envelopes and do not grasp the benefit of incorporating all technologies into one model. Additionally, the industry is lagging in the adaptation of BIM technologies, since, as of today, only one company in the world is BIM level-2 certified. Witteveen+Bos recognises the potential of smart systems and is developing many innovative software solutions. In this thesis, as the objective stated, a conceptual partly BIM level-3 excavation site design tool has been developed. The developed tool, integrates parametric design with Plaxis, GIS and RockWorks. The developed tool helps stakeholders to visually explore many design solutions in a short amount of time, based on the costs, MKI, structural- and environmental requirements and the characteristics of the surroundings. The name SET (Smart Engineering Tool) was given to this tool.Three essential boundary conditions are distinguished for the design of an excavation pit. Soil Layers, groundwater levels and the surrounding buildings. These boundary conditions impose loads and requirements on the excavation pit. The way the groundwater can be kept out determines mostly the costs. For this reason, SET works-out designs with a natural impermeable clay layer, an artificial underwater concrete floor or an artificial impermeable gel layer. Additionally, designs with different retaining walls and grout anchors or struts are worked-out. The design of an excavation pit must meet structural and environmental requirements. A vertical, horizontal and moment equilibrium must hold in the excavation pit. In urban areas, the most important concern is avoiding inadmissible damage or hindrance to adjacent structures, because the surrounding buildings are owned by third parties and deformations, causing damage to these buildings, happen quick. For this reason, the design of the excavation pit must meet the settlement requirements of the surrounding buildings. For each design, “Economisch Meest Voordelige Inschrijving” (EMVI) (Economically Most Attractive Tender) scores are used to quantify each design on durability, the impact on the surroundings, hindrance and risk. EMVI in combination with the cost estimates is used to find the design with the best cost to quality ratio. Rijkswaterstaat has determined a “Milieu Kosten Indicator” (MKI) (Environmental Cost Indicator) value for each building material. In this thesis, this value is used to quantify the environmental impact of a designAn analysis was made on the capabilities that a design tool should have. A literature study was performed on the BIM technologies. From this analysis six BIM technologies are included in the development of the tool. These are: parametric design, algorithmic design, collaborative design, central repository, interoperability and standardization. Additionally, for the development of the design tool, different programming languages and development platforms were considered. A combination of Python and JavaScript together with the Web-based Graphics Library (WebGL) was found to be most suitable. A Python back-end processes the data and runs a design algorithm, while the web-based front-end facilitates collocative design and 3D visualisations. The sever, created with the Python module Django, is used for the communication between Python and JavaScript. The JavaScript module Three.js is used to utilize the WebGL capabilities. The development of the design tool, called SET (Smart Engineering Tool), is based on the method of rapid prototyping. This includes prototyping, test and review, refine and iterate. The prototyping process is split into four stages: (1) Interoperability and Standardization, (2) Design algorithm, (3) Collaboration, Interaction and 3D Visuals and (4) Integration. In each of these stages, an essential part of SET was developed. SET is interoperable with Plaxis 2D, a geotechnical finite element program and uses the input of GIS and RockWorks. SET’s internal design algorithm determines what excavation site designs should be calculated by Plaxis. This is based on user settings, and the boundary conditions, surrounding and environmental requirements. The boundary conditions are extracted from GIS files and from RockWorks models. The surrounding buildings are extracted from GIS, and RockWorks supplies the soil stratification. The design tool interprets these boundary conditions and standardizes the data. All data is transferred to a parallel computer, where finite element calculations are performed in Plaxis. Plaxis calculates the vertical, horizontal and moment equilibria and the deformations of the soil. SET analyses the successful Plaxis results and performs a unity check on bending moments in the retaining walls together with an analysis on the settlements requirements of the surrounding buildings. SET is tested and reviewed, by a geotechnical expert and an engineer, with two test cases. The results of these tests cases were analysed and validated. The functionalities and the user-friendliness of the tool have been scrutinized. Based on these tests, SET was reviewed, and refinements and iterations of the design tool emerged. During the development of SET, Witteveen+Bos was working on a tender. The tendered project is a design of a bus lane next to the existing train tracks and is called “Hoogwaardig Openbaar Vervoer in het Gooi” (high quality public transport), in short “HOV in ‘t Gooi”. The currently level intersection of the bus lane with the ‘Oosterengweg’ was used to test SET with two test cases. A tunnel for the Oosterengweg underneath the train track and bus lane, was the first case and a tunnel for the train tracks and bus lane underneath the Oosterengweg, was the second case. The first case, was a similar solution as the final tender design of Witteveen+Bos. The second case however, was an “out of the box” design and which was initially deemed unfeasible by Witteveen+Bos. The testcases took around one hour to prepare in SET. For both test cases, the corresponding Plaxis calculations took around a day of computation time to finish. As a result, SET found many feasible designs for both test cases, in two days. The design of the train and bus tunnel, that was deemed unfeasible, was found to be feasible and almost a third of the cost compared to the Oosterengweg tunnel. However, it must be noted that the costs to redirect the train tracks and the maximum obstruction time of the train was not included in these designs. It can be concluded that SET is partly BIM level-3. The foundations of the SET lie in BIM level-1 and -2. The design tool supports 2D and 3D visuals and parametric design is used in an object-oriented manner for the design of the excavation pit. The tool does not use the all-enveloping BIM standard IFC. However, the design tool does use standardization. Based on requirements from the surroundings and the environment, SET helps to explore a large number of designs in a short period of time and visualizes different designs in 3D and in an interactive graph. The data is managed from a server, which acts as a central repository. Stakeholders can access this server from a web browser and are able to analyse their preferred designs within the extended design space. SET shows 6 major benefits. (1) During the conceptual design phase, the feasibility of designs in a large design space can be analysed without being labour intensive and within a short amount of time. (2) The decisions concerning the final design can be postponed to the very end. Thus, designs that would conventionally be deemed unfeasible in the conceptual stage can emerge as feasible in later stages. (3) The possibility of a collaborative platform stimulates shared and parallel decision making. Each stakeholder can incorporate various requirements, limitations and responsibilities into the model, which utilizes the knowledge and expertise of each stakeholder. (4) The design tool can be used from the very beginning in meetings and discussions with clients to convey information in real time, by the means of 3D visuals. Clients can be granted remote access to SET and evaluate design solutions from the comfort of their office, without sharing valuable scripts and sensitive or private data. (5) Calculations can be processed automatically on a parallel server without the supervision of an engineer. (6) SET integrates multiple design tools like GIS, RockWorks and Plaxis. Overall, SET reduces the required labour to create a design and increases the productivity of an engineer. This reduces the costs of the design process and allows engineers to create “out of the box designs”. Civil Engineering | Hydraulic StructuresCivil Engineering | Hydraulic Engineerin
Environmental impacts during the operational phase of residential buildings
No full textTo date, the focus in the field of sustainable building has been on new building design. However, existing residential buildings inflict great environmental burden through three causes: continuous energy consumption, regular building maintenance and replacements. This publication analyses and compares these three causes of environmental burden and shows that material resources needed for replacements generally have a limited potential to reduce environmental impact. Reducing energy consumption for climate control and electrical appliances is much more effective. According to the author, sustainable measures should be tested for shifts in the kind of environmental impact caused due to the use of alternative types of energy resources and altered material quantities. The sustainability of the electricity supply is essential to decrease the total environmental impact of the residential building stock.Sustainable and Healthy HousingOTB Research Institut
Cytochrome oxidase subunit VI of Trypanosoma brucei is imported without a cleaved presequence and is developmentally regulated at both RNA and protein levels
No full textMitochondrial respiration in the African trypanosome undergoes dramatic developmental stage regulation. This requires co-ordinated control of components encoded by both the nuclear genome and the kinetoplast, the unusual mitochondrial genome of these parasites. As a model for understanding the co-ordination of these genomes, we have examined the regulation and mitochondrial import of a nuclear-encoded component of the cytochrome oxidase complex, cytochrome oxidase subunit VI (COXVI). By generating transgenic trypanosomes expressing intact or mutant forms of this protein, we demonstrate that COXVI is not imported using a conventional cleaved presequence and show that sequences at the N-terminus of the protein are necessary for correct mitochondrial sorting. Analyses of endogenous and transgenic COXVI mRNA and protein expression in parasites undergoing developmental stage differentiation demonstrates a temporal order of control involving regulation in the abundance of, first, mRNA and then protein. This represents the first dissection of the regulation and import of a nuclear-encoded protein into the cytochrome oxidase complex in these organisms, which were among the earliest eukaryotes to possess a mitochondrion
Non-Linear Finite Element Analyses of Existing Reinforced Concrete Bridge Beams
No full textThree years ago, the Dutch Ministry of Infrastructure and the Environment initiated a project to re-evaluate the carrying capacity of existing bridges and viaducts (e.g. reinforced and pre-stressed concrete beams and slabs). Due to the increase of traffic and the reallocation of emergency lanes to traffic lanes, the safety verification of some concrete structures are not satisfied if the usual analytical procedures are followed. Nonlinear finite element analyses (NLFEA) are considered as one of the alternatives for the verification of the structural carrying capacity. Building codes hardly provide specific guidance on how NLFEA should be carried out and reported. Within the project guidelines for NLFEA have been developed in order to reduce model and user factors. The aim of the project well fits with the philosophy of the new Model Code 2010 (MC2010) that proposes analytical and numerical calculation methods for the evaluation of the design resistance of reinforced concrete (RC) structures. In the paper four reinforced concrete beams, characterized by different failure modes, have been analyzed through the analytical and numerical procedures proposed by the Model Code 2010 and following the Dutch guidelines. The results obtained have been compared with the experimental results available in literature. Furthermore in order to focus on the main sensitive parameters that influence the results obtained from NLFEA and to obtain reliable and, at the same time, safe results, parametric studies have also been carried out on the beams. The main indications of the guidelines for reinforced concrete beams are presented in the paper.Structural EngineeringCivil Engineering and Geoscience
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No full textEditorialGreen Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Applied Mechanic
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